The health and stability of the dental enamel require that saliva exists as a supersaturated solution of calcium phosphate. This supersaturation is stabilized by two groups of phosphorylated polypeptides. In the initial phase of this proposal we have determined the complete primary structure of these two groups of proteins, statherin and the anionic proline rich proteins, the PRP's, and have localized the site of precipitation-inhibition in these molecules. We are now embarking upon comparative amino acid sequence studies to gain insights into the evolution and biosynthesis of these novel proteins and are expanding our active site localization studies by synthesizing analogs of statherin and the PRP's. These synthetic analogs will function as molecular probes in elucidating the molecular mode of action of the salivary proteins-inhibitors and may become potential clinical tools in studying dental disease. Another main objective of competitive newal includes conformational analyses on the human salivary protein inhibitors, synthetic peptides of theinhibitory and/or calcium binding regions and their peptide analogs using fluorescence spectroscopy and multinuclear resonance spectroscopy. These latter studies shold provide an accurate understanding of the mechanism of protein-calcium interaction.